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63 Cards in this Set
- Front
- Back
Pharmacology
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The science dealing with interactions between living systems and molecules, especially chemicals introduced from outside the system
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Medical Pharmacology
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Science of materials: used to prevent, diagnose, and treat disease; that cause disease; used as molecular probes for the study of normal biochemistry and physiology
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Toxicology
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Branch of pharmacology that deals with the undesirable effects of chemicals in biologic systems
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Drug
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Any small molecule that, when introduced into the body, alters the body's function by interactions at the molecular level
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Pharmacodynamics
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Responsiveness of receptors to drugs and the mechanism by which these effects occur. "What a drug does to the body"
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Pharmacokinetics
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Absorption, distribution, metabolism and excretion of inhaled or injected drugs. "What the body does to a drug"
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Stereochemistry
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Study of how molecules are structured in three dimensions
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Chirality
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Unique subset of stereochemistry designating molecules that have a center (or centers) of three dimensional asymmetry. Chirality is the structural basis for enantiomerism
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Enantiomers
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A pair of molecules existing in 2 forms that are mirror images of one another but cannot be superimposed (are of opposite shapes)
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Stereoselectivity
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The direction in which they rotate polarized light; clockwise rotation=dextrorotary, d+ or levorotary l- (Ex. Right and Left hand)
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Stereospecificity
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The absolute configuration is specified by the designation of sinister (S) or rectus (R)
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Racemic Mixture
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When 2 enantiomers are present in equal proportions (50:50 mixture) Ex. Epi, Ketamine
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Absorption
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Movement into the body from the site of administration
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Distribution
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Movement between different parts of the body
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Biotransformation
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Alters activity of drug and may prepare it for excretion
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Excretion
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Movement out of the body
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Name the 4 major mechanisms by which drugs move across barriers
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Aqueous diffusion (passive)
Lipid diffusion (passive) Active Transport Facilitated diffusion |
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Aqueous Diffusion (Passive)
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Only drugs of very small molecular weight (100-150) can diffuse across epithelial membranes (cornea, GI tract, bladder). Epithelial cells are connected by tight junctions that do not permit larger molecules to enter. Most capillaries have very large aqueous pores allowing molecules as large as 20-30,000 to enter
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Lipid Diffusion (Passive)
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Movement across cell membranes by solution in the lipids of the membrane, with passive transfer across the lipid driven by a concentration gradient. Drugs with higher lipid solubilities (relative to water solubility) favor this mode of transfer. Move down concentration grandient High--Low
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Fick's Law of Diffusion (magnitude of flux)
*Know proportional relationships |
J magnitude of flux = P Permeability coefficient x A Area across which diffusion occurs x (C1-C2) Concentration gradient divided by membrane thickness x square root of molecular weight
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Lipid solubility (permeability coefficient) is greatly influenced by what?
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Degree of ionization
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Which type of molecule crosses the lipid membrane more readily: Unionized (uncharged) or Ionized (charged)
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Unionized (uncharged)
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Many drugs are either weak bases or weak acids. Describe their relationship pH
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The pH of the environment greatly influences the degree of ionization and thus solubility
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At an alkaline pH, acidic drugs tend to be...
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Highly ionized (charged)
Ex. sodium thiopental |
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At an acidic pH, alkaline drugs tend to be...
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Highly ionized (charged)
Ex. local anesthetics |
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Henderson-Hasselbach
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Equation describing the degree of ionization in a particular pH environment
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pKa
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the pH at which a molecule is 50% ionized and 50% unionized
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Acids
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Proton donors
pH = pKa + log A- (acid) divided by HA (protonated acid) Ex. Barbiturates, ASA |
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Bases
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Proton donors
pH = pKa + log B (base) divided by BH+ (protonated base) Ex. Local anesthetics, opioids |
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pH = A- divided by HA
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A- (unprotonated, charged, ionized) divided by
HA (protonated, uncharged, unionized) |
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pH = B divided by BH+
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B (unprotonated, uncharged, unionized) divided by
BH+ (protonated, charged, ionized) |
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pKa 1 for Acid
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pKa 1 = .5/.5
Acid (unprotonated, charged, ionized) over (protonated, uncharged, unionized) |
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pKa -1 for Acid
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pKa -1 = .1/.9
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pKa +1 for Acid
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pKa +1 = .9/.1
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pKa 1 for Base
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pKa 1 = .5/.5
Base (unprotonated, uncharged, unionized) over (protonated, charged, ionized) |
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pKa -1 for Base
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pKa -1 = .1/.9
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pKa +1 for Base
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pKa +1 = .9/.1
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Ion trapping
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Concentration difference of total drug can develop on 2 sides of a membrane that separates fluids with different pHs. A drug enters a lipid membrane through a pH environment that renders the drug uncharged---after crossing the membrane into a more acidic environment, the drug becomes charged and thus unable to go back across the membrane.
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Give 2 examples of ion trapping in the body
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1. Oral administration of weak bases (opioids) becomes highly ionized (charged) in the stomach and thus "trapped" in the intestine
2. Some drugs cross the maternal placenta into the fetal circulation which has a lower pH. The drugs become highly ionized (charged) and thus "trapped" within the fetal circulation |
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Active transport
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Transports molecules across membranes in an energy-dependent process. The process is molecule specific, saturable, and can occur against a concentration gradient. There is a limit to the effectiveness of dose
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Facilitated diffusion
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Similar to active transport in that it is carrier-mediated, specific, and saturable but it does not require energy and cannot transport against a concentration gradient. Pinocytosis (receptor-mediated endocytosis) is an example of facilitated diffusion. Also insulin release b/c it doesn't require energy, but needs a 2nd messenger
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VRG
CO BM Onset |
Vessel Rich Group-1
CO-75% BM-10% Brain, heart, liver, kidney, endocrine glands Onset-rapid |
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MG
CO BM Onset |
Muscle Group-2
CO-19% BM-50% Muscle, skin Onset-rapid |
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FG
CO BM Onset |
Fat Group-3
CO-6% BM-20% Fat Onset-Slower |
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VPG
CO BO Onset |
Vessel Poor Group-3
CO-less than 1% BM-20% Bone, ligament, cartilage Onset-Slowest |
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Which compartment are drugs eliminated from?
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Central compartment
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k
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Represents the different rate constants for intercompartmental transfer of drug as well as the elimination rate constant. Movement of drug
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What are the pharmacokinetic compartment models useful for?
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Explaining the changes in plasma concentration that occur after a drug is administered. Compartments are hypothetical and cannot actually be measured
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Hypnosis
Hypnotic drug |
Sleep
Puts pt to sleep |
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Drug in Body
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1/2 Life
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Drug in Plasma
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1/2 Time
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Rapid Distribution Phase
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t 1/2 pie
Represents the equilibrium within the VRG referred to as peak half-time |
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Slower Distribution (Redistribution) Phase
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t 1/2 alpha
Represents the distribution from the circulation (central compartment) to peripheral tissues (peripheral compartment); referred to as distribution half-time |
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Elimination Phase
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t 1/2 beta
Time necessary for the plasma concentration of the drug to decline 50% during the elimination phase. This time is derived by measuring the time between any two points that differ by a 2-fold plasma concentration |
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t 1/2 beta is directly proportional to...
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the Volume of distribution of the drug
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t 1/2 beta is inversely proportional to...
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the Clearance of the drug
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Renal or hepatic disease will alter...
which effects... |
-Volume of distribution and Clearance
-Effects t1/2 beta |
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True or False
t 1/2 beta is dependent on the dose of the drug administered |
False
t 1/2 beta is independent of the dose of drug administered (1st-order kinetics only) |
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Elimination half-life
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The time necessary to eliminate 50% of the total drug dose from the entire body (not just the plasma). Drugs can be stored in the various compartments of the body thereby decreasing plasma concentration
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# of half-times vs. change in drug concentration
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1-50%, 2-75%, 3-87.5%, 4-93.8%, 5-96.9%, 6-98.4%
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Less than 5 1/2 times and patient not awake...
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give reversal agent
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Context-sensitive half-time
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Time necessary for the plasma drug concentration to decrease by 50% (or any other percent) after discontinuing a continuous infusion of a specific duration (context refers to infusion duration)
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Name 3 effects of Context-sensitive half-time
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1. circumvents limitations of t 1/2 beta in describing post-transfusion central compartment drug pharmacokinetics
2. Effect of distribution on plasma drug concentrations varies in magnitude and direction over time and depends on the drug concentration gradients between various compartments 3. Considers the combined effects of distribution and metabolism as well as duration of continuous IV administration on drug pharmacokinetics |